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Intravenous immune globulin suppresses angiogenesis in mice and humans

Signal Transduction and Targeted Therapy 2016年第1期1卷 141-148页

作者： Reo Yasuma Valeria Cicatiello Takeshi Mizutani Laura Tudisco Younghee Kim Valeria Tarallo Sasha Bogdanovich Yoshio Hirano Nagaraj Kerur Shengjian Li Tetsuhiro Yasuma Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide.greco Arturo Brunetti Balamurali K Ambati Sevim Barbasso Helmers Ingrid e Lundberg Ondrej Viklicky Jeanette HW Leusen J Sjef Verbeek Bradley D Gelfand Ana Bastos-Carvalho Sandro De Falco Jayakrishna Ambati Department of Ophthalmology and Visual Sciences University of KentuckyLexingtonKYUSA Department of Ophthalmology Nagoya University Graduate School of MedicineNagoyaJapan Angiogenesis Lab Institute of Genetics and Biophysics—CNRNaplesItaly Bio-Ker MultiMedica GroupNaplesItaly Department of Physiology University of KentuckyLexingtonKYUSA Department of Advanced Biomedical Sciences University of Naples‘Federico II’NaplesItaly CeINGe—Biotecnologie Avanzate s.c.ar.l.NaplesItaly Department of Ophthalmology and Visual Sciences Moran Eye CenterUniversity of Utah School of MedicineSalt Lake CityUTUSA Department of Ophthalmology Veterans Affairs Salt Lake City Healthcare SystemSalt Lake CityUTUSA Rheumatology Unit Department of MedicineKarolinska InstitutetKarolinska University HospitalStockholmSweden Department of Nephrology Institute for Clinical and Experimental MedicinePrague 4Czech Republic Immunotherapy Laboratory Laboratory for Translational ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands Department of Human Genetics Leiden University Medical CenterLeidenThe Netherlands Department of Biomedical engineering University of KentuckyLexingtonKYUSA Department of Microbiology Immunologyand Molecular GeneticsUniversity of KentuckyLexingtonKYUSA IRCCS MultiMedica MilanoItaly

Human intravenous immune globulin(IVIg),a purified IgG fraction composed of~60%IgG1 and obtained from the pooled plasma of thousands of donors,is clinically used for a wide range of *** biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG(IgG)Fc ***,we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI,a high-affinity receptor for *** we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases,namely,neovascular age-related macular degeneration,corneal neovascularization,colorectal cancer,fibrosarcoma and peripheral arterial ischemic *** was mediated by the Fc region of IVIg,required FcγRI and had similar potency in transgenic mice expressing human Fcγ***,IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel *** data place IVIg,an agent approved by the US Food and Drug Administration,as a novel angioinhibitory drug in doses that are currently administered in the clinical *** addition,they raise the possibility of an unintended effect of IVIg on blood vessels.

关键词： doses inhibited degeneration

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Neuroprotective and anti-inflammatory effects of a therapy combining agonists of nicotinic α7 and σ1 receptors in a rat model of Parkinson’s disease

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Neural Regeneration Research 2021年第6期16卷 1099-1104页

作者： steven Vetel Laura Foucault-Fruchard Claire Tronel Frédéric Buron Jackie Vergote Sylvie Bodard Sylvain Routier Sophie Sérrière Sylvie Chalon UMR 1253 iBrainUniversitéde ToursInsermToursFrance CHU Tours Service pharmacieToursFrance Institut de Chimie Organique et Analytique ICOAUMR CNRS 7311Universitéd’OrléansOrléansFrance

To date there is no treatment able to stop or slow down the loss of dopaminergic neurons that characterizes Parkinson’s *** was recently observed in a rodent model of Alzheimer’s disease that the interaction between the α7 subtype of nicotinic acetylcholine receptor(α7-nAChR)and sigma-1 receptor(σ1-R)could exert neuroprotective effects through the modulation of neuroinflammation which is one of the key components of the pathophysiology of Parkinson’s *** this context,the aim of the present study was to assess the effects of the concomitant administration of N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide(PHA)543613 as an α7-nAChR agonist and 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate(PRe)-084 as aσ1-R agonist in a well-characterized 6-hydroxydopamine rat model of Parkinson’s *** animals received either vehicle separately or the dual therapy PHA/PRe once a day until day 14 *** no effect was noticed in the amphetamine-induced rotation test,our data has shown that the PHA/PRe treatment induced partial protection of the dopaminergic neurons(15-20%),assessed by the dopamine transporter density in the striatum and immunoreactive tyrosine hydroxylase in the substantia ***,this dual therapy reduced the degree of glial activation consecutive to the 6-hydroxydopamine lesion,i.e,the 18 kDa translocation protein density and glial fibrillary acidic protein staining in the striatum,and the CD11b and glial fibrillary acidic protein staining in the substantia ***,this study reports for the first time that concomitant activation of α7-nAChR andσ1-R can provide a partial recovery of the nigro-striatal dopaminergic neurons through the modulation of microglial *** study was approved by the Regional ethics Committee(CeeA Val de Loire n°19)validated this protocol(Authorization N°00434.02)on May 15,2014.

关键词： 6-hydroxydopamine astrocytes microglial activation neurodegeneration neuroinflammation nicotinicα7 receptor Parkinson’s disease PHA 543613 PRe-084 sigma-1 receptor

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Gelatin degradation assay reveals MMP-9 inhibitors and function of O-glycosylated domain

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World Journal of Biological Chemistry 2011年第1期2卷 14-24页

作者： Jennifer Vandooren Nathalie Geurts erik Martens Philippe e Van den Steen steven De Jonghe Piet Herdewijn Ghislain Opdenakker Laboratory of Immunobiology Rega Institute for Medical Research University of Leuven Minderbroederstraat 10 Leuven B-3000 Belgium Medicinal Chemistry Rega Institute for Medical Research University of Leuven Minderbroederstraat 10 Leuven B-3000 Belgium

AIM: To establish a novel, sensitive and high-throughput gelatinolytic assay to define new inhibitors and compare domain deletion mutants of gelatinase B/matrix metalloproteinase (MMP)-9. MeTHODS: Fluorogenic Dye-quenched (DQ)TM-gelatin was used as a substrate and biochemical parameters (substrate and enzyme concentrations, DMSO solvent concentrations) were optimized to establish a highthroughput assay system. Various small-sized libraries (ChemDiv, InterBioScreen and ChemBridge) of hetero-cyclic, drug-like substances were tested and compared with prototypic inhibitors. ReSULTS: First, we designed a test system with gelatin as a natural substrate. Second, the assay was validated by selecting a novel pyrimidine-2,4,6-trione (barbitu- rate) inhibitor. Third, and in line with present structural data on collagenolysis, it was found that deletion of the O-glycosylated region significantly decreased gelatinolytic activity (kcat/kM ± 40% less than full-length MMP-9). CONCLUSION: The DQTM-gelatin assay is useful in high-throughput drug screening and exosite targeting. We demonstrate that flexibility between the catalytic and hemopexin domain is functionally critical for gelatinolysis.

关键词： exosite inhibitors Fluorogenic substrate Gelatin High-throughput screening assays Matrix metalloproteinase-9 Substrate specificity

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Fault Detection of Networked Control Systems Subject to Access Constraints and Random Packet Dropout

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自动化学报 2009年第9期35卷 1230-1234页

作者： WANG Yong-Qiang Ye Hao DING steven WANG Gui-Zeng Department of Automation Tsinghua National Laboratory for Information Science and Technology (TNList) Tsinghua University Beijing 100084 P. R. China Institute for Automatic Control and Complex Systems University of Duisburg-Essen Duisburg 47057 Germany

In this paper, the problem of fault detection is addressed for networked control systems (NCSs) subject to both access constraints and random packet dropout, which to the best of our knowledge has not been considered before. Both residual generation and residual evaluation as well as false alarm computation of the designated threshold are given. First, based on a deterministic formulation, residual generation is carried out in the periodic system framework. Then, residual evaluation is achieved by making full use of the stochastic properties of the random packet dropout. Finally, performance evaluation of the designated threshold, i.e., the computation of false alarm rate, is fulfilled with the assistance of Chebyshev s inequality. Simulation results are given to illustrate effectiveness of the proposed method.

关键词：故障检测网路控制接入约束残差

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Neurosurgical and pharmacological management of dystonia

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World Journal of Psychiatry 2024年第5期14卷 624-634页

作者： Ali Ahmed Mohamed steven Faragalla Asad Khan Garrett Flynn Gersham Rainone Phillip Mitchell Johansen Brandon Lucke-Wold Charles e Schmidt College of Medicine Florida Atlantic UniversityBoca RatonFL 33431United States Department of Neurosurgery and Brain Repair University of South FloridaTampaFL 33606United States Department of Neurosurgery University of FloridaGainesvilleFL 32611United States

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal *** types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given *** most patients afflicted with these disorders,an exact cause is rarely identified,so treatment mainly focuses on symptomatic *** agents,such as oral anticholinergic administration and botulinum toxin injection,play a major role in the initial treatment of *** more severe and/or refractory cases,focal areas for neurosurgical intervention are identified and targeted to improve quality of *** brain stimulation(DBS)targets these anatomical locations to minimize dystonia *** ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to *** management options grant providers and patients the ability to weigh the benefits and risks for each individual patient *** review article explores these pharmacological and neurosurgical management modalities for dystonia,providing a comprehensive assessment of each of their benefits and shortcomings.

关键词： Botulinum toxin Magnetic resonance imaging-guided focused ultrasound Surgical ablation Deep brain stimulation Peripheral denervation surgery Antipsychotics

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Organizational Behavior steven L. McShane 3rd ed.; international ed.

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2005年

作者： steven L. McShane

Subtitle on cover: emerging realities for the workplace revolution.

ISBN: (数字)0072931477

ISBN: (纸本)0072931477

Subtitle on cover: emerging realities for the workplace revolution.

关键词： Organizational behavior.

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激光原位角膜磨镶术和屈光性角膜消融术后伤口愈合反应—个体化激光视力矫正后难以控制的生物学多样性和效应

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美国医学会眼科杂志（中文版） 2002年第1期14卷 9-15,49页

作者： steven e.Wilson 金红颖等 FromtheDepartmentsofOphthalmology UniversityofWashingtonSeattle

伤口愈合反应中的生物学多样性被认为是限制屈光手术，比如激光原位角膜磨镶术和屈光性角膜消融术的结果可预测性的主要因素。角膜伤口的愈合是影响角膜地形图或波阵面引导的准分子激光切削以达到最优视力成功的关键因素。这是因为维持... 详细信息

伤口愈合反应中的生物学多样性被认为是限制屈光手术，比如激光原位角膜磨镶术和屈光性角膜消融术的结果可预测性的主要因素。角膜伤口的愈合是影响角膜地形图或波阵面引导的准分子激光切削以达到最优视力成功的关键因素。这是因为维持个体化切削后的细微特点的重要性、上皮增生和基质的重新塑型倾向掩盖了这些特点。角膜的伤口愈合反应是极其复杂的。出现在上皮损伤反应中的角膜细胞的凋亡是在伤口愈合时最早可观察到的情况，也因此成为药物介入治疗的最佳靶位。改变手术技术的设计可以限制角膜细胞的凋亡和随后出现在伤口愈合中的一些情况。串联的异常可能是造成角膜疾病的病因。比如，最近的数据表明对角膜细胞的凋亡／有丝分裂平衡的扰动可能是部分患者形成圆锥角膜的潜在因素。

关键词：激光原位角膜磨镶术屈克性角膜消融术伤口愈合反应角膜伤口视力矫正角膜疾病

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Using a temporal phylogenetic method to harmonize familyand genus-level classification in the largest clade of lichen-forming fungi

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Fungal Diversity 2017年第3期84卷 101-117页

作者： Pradeep K.Divakar Ana Crespo ekaphan Kraichak steven D.Leavitt Garima Singh Imke Schmitt H.Thorsten Lumbsch Departamento de Biología Vegetal II Facultad de FarmaciaUniversidad Complutense de Madrid28040 MadridSpain Department of Botany Faculty of ScienceKasetsart UniversityBangkokThailand Department of Biology and M.L.Bean Life Science Museum Brigham Young University4102 Life Science BuildingProvoUT 84602USA Department of Biological Sciences Institute of EcologyEvolution and DiversityGoethe Universitat and Senckenberg Biodiversity and Climate Research Centre(BiK-F)Frankfurt am MainGermany Science&education The Field MuseumChicagoILUSA

Although classification at supra-specific ranks is inherently arbitrary,comparable taxonomic ranks within clades can facilitate more consistent classifications and objective comparisons among *** circumscriptions of the hyper-diverse lichen-forming fungal family Parmeliaceae and widely different generic circumscriptions among authors have been *** this study,we use a recently developed temporal approach that uses timecalibrated chronograms to identify temporal bands for specific ranks in Parmeliaceae and allied groups with the overarching goal of establishing a consistent,stable classification.A data set of 330 species,representing 73 genera in the family and 52 species of related families was used to address the circumscription of Parmeliaceae and its genera following the proposed temporal *** on the results of this study,we propose a revised,temporal-based classification for Parmeliaceae,including all clades that share a common ancestor 102.13–112.88 Ma for families and a time window of 29.45–32.55 Ma for *** of the currently accepted genera in Parmeliaceae were supported in their current *** subfamilies are accepted within Parmeliaceae:Protoparmelioideae Divakar et ***.,including Protoparmelia and the resurrected genus Maronina,and Parmelioideae,including the bulk of genera in the *** new genus Austromelanelixia Divakar et *** proposed to accommodate a clade of southern Hemisphere species previously included in *** and tentatively Dolichousnea are resurrected as genera separate from *** following genera are reduced to synonymy:Allocetraria,Cetrariella,Usnocetraria,and Vulpicida with Cetraria;Arctocetraria,Cetreliopsis,Flavocetraria,Kaernefeltia,Masonhalea,Tuckermanella,and Tuckermannopsis with Nephromopsis;and the lichenicolous genera Nesolechia and Raesaenenia with the lichen-forming genera Punctelia and Protousnea,respectively.A total of 47 new combinations and

关键词： Ascomycota Gypsoplacaceae Lecanorales Lichenized fungi Parmeliaceae Phylogeny Protoparmelia Taxonomy Taxonomicranks

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控制系统网络安全观念及实践

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软件 2010年第5期31卷 22-24页

作者： Matthew e.Luallen steven e.Hamburg CCIe CISSPGIAC Pe encari

日前进行的一项关于工业控制系统网络安全评估的调查，收到近200份的答卷。虽然答卷中的一些趋势是事先预计到的，然而也有一些出人意料或相当惊人的反应。本文从简单的观察入手，并对预期不足的反应和趋势进行总结，以便我们对调查答... 详细信息

日前进行的一项关于工业控制系统网络安全评估的调查，收到近200份的答卷。虽然答卷中的一些趋势是事先预计到的，然而也有一些出人意料或相当惊人的反应。本文从简单的观察入手，并对预期不足的反应和趋势进行总结，以便我们对调查答复进行分析。

关键词：控制系统网络安全观念网络安全评估工业控制系统反应答复

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Bayesian geological and geophysical data fusion for the construction and uncertainty quantification of 3D geological models

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Geoscience Frontiers 2021年第1期12卷 479-493页

作者： Hugo K.H.Olierook Richard Scalzo David Kohn Rohitash Chandra ehsan Farahbakhsh Chris Clark steven M.Reddy R.Dietmar Müller School of earth and Planetary Sciences Curtin UniversityGPO Box U1987PerthWA6845Australia Centre for Translational Data Science University of SydneyNSW2006SydneyAustralia Sydney Informatics Hub University of SydneyNSW2006SydneyAustralia earthByte Group School of GeosciencesUniversity of SydneyNSW2006SydneyAustralia Timescales of Mineral Systems and John de Laeter Centre Curtin UniversityGPO Box U1987PerthWA6845Australia School of Mathematics and Statistics University of New South WalesSydneyNSW2052Australia Department of Mining engineering Amirkabir University of Technology(Tehran Polytechnic)TehranIran

Traditional approaches to develop 3D geological models employ a mix of quantitative and qualitative scientific techniques,which do not fully provide quantification of uncertainty in the constructed models and fail to optimally weight geological field observations against constraints from geophysical ***,using the Bayesian Obsidian software package,we develop a methodology to fuse lithostratigraphic field observations with aeromagnetic and gravity data to build a 3D model in a small(13.5 km×13.5 km)region of the Gascoyne Province,Western *** approach is validated by comparing 3D model results to independently-constrained geological maps and cross-sections produced by the Geological Survey of Western *** fusing geological field data with aeromagnetic and gravity surveys,we show that 89%of the modelled region has>95%certainty for a particular geological unit for the given model and *** boundaries between geological units are characterized by narrow regions withertainty,which are typically 400-1000 m wide at the earth's surface and 500-2000 m wide at ***~4 km depth,the model requires geophysical survey data with longer wavelengths(e.g.,active seismic)to constrain the deeper *** Obsidian was originally built for sedimentary basin problems,there is reasonable applicability to deformed terranes such as the Gascoyne ***,modification of the Bayesian engine to incorporate structural data will aid in developing more robust 3D ***,our results show that surface geological observations fused with geophysical survey data can yield reasonable 3D geological models with narrow uncertainty regions at the surface and shallow subsurface,which will be especially valuable for mineral exploration and the development of 3D geological models under cover.

关键词： Capricorn orogen Machine learning Bayesian inference Markov chain Monte Carlo Solid earth Mineral exploration

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